Preferential metabolic activation of subcortical brain areas by acute administration of nicotine to rats.
Cerebral metabolic and behavioral effects of acutely administered nicotine were measured in rats in relation to dose. Nicotine 0.1, 1, or 10 mg/kg or vehicle was administered intraperitoneally to 3-month-old male Fischer-344 rats that had been pretreated with hexamethonium bromide 5 mg/kg i.p. to reduce peripheral autonomic effects. Regional CMRglc (rCMRglc) values were measured, using the quantitative autoradiographic [14C]-2-deoxy-D-glucose method, in 71 brain regions, beginning 3 min after nicotine or vehicle administration. Intensity of body tremor, scored by a blinded rater, was dose related and peaked at 3 min after nicotine injection. rCMRglc rose in a dose-related manner: Nicotine 0.1 mg/kg had no significant effect in any region, whereas 1 mg/kg elevated rCMRglc significantly in 21 regions (mean rise 20%) and 10 mg/kg produced generalized (56 regions) and greater (mean rise 50%) increases in rCMRglc. Nicotine 1 mg/kg activated thalamic nuclei, cerebellum, geniculate nuclei, superior colliculus, median raphe, reticular formation, and the habenulointerpeduncular pathway, but was without effect in the telencephalon. Effects of nicotine in the hindbrain were related anatomically to reported distributions of [3H]nicotine and [3H]acetylcholine but not [125I]alpha-bungarotoxin binding sites, implying that the former ligands label functional nicotine receptors. The pattern of change in rCMRglc after nicotine administration suggests that its cognitive effects in humans are due to augmented arousal/attention and visual processing rather than to direct neocortical or hippocampal activation.
McNamara
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Laboratory of Neurosciences, National Institute on Aging, Bethesda, Maryland.
Larson
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Rapoport
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Soncrant
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014018:Tissue Distribution; D014202:Tremor / Q000139:chemically induced
D001786:Blood Glucose; D009538:Nicotine; D005947:Glucose